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Background: Bronchoscopic lung volume reduction using endobronchial coils is a new treatment for patients with severe emphysema. To date, the benefits have been modest and have been suggested to be much larger in patients with severe hyperinflation and nonmulti-comorbidity. Objective: We aimed to evaluate the efficacy and safety of endobronchial coil treatment in a randomized multicenter clinical trial using optimized patient selection. Method: Patients with severe emphysema on HRCT scan with severe hyperinflation (residual volume [RV] ≥200% predicted and RV/total lung capacity [TLC] >55%) were randomized to coil treatment or control. Primary outcome measures were differences in the forced expiratory volume in 1 s (FEV1) and St George’s Respiratory Questionnaire (SGRQ) total score at 6 months. Results: Due to premature study termination, a total of 120 patients (age 63 ± 7 years, FEV1 29 ± 7% predicted, RV 251 ± 41% predicted, RV/TLC 67 ± 6%, and SGRQ 58 ± 13 points), instead of 210 patients, were randomized. At study termination, 91 patients (57 coil and 34 control) had 6-month results available. Analyses showed significantly greater improvements in favor of the coil group. The increase in FEV1 was greater in the coil group than that in the control group by + 10.3 [+4.7 to +16.0] % and in SGRQ by −10.6 [−15.9 to −5.4] points. At study termination, there were 5 (6.8%) deaths in the coil cohort reported. Conclusion: Despite early study termination, coil treatment compared to control results in a significant improvement in the lung function and quality of life benefits for up to 6 months in patients with emphysema and severe hyperinflation. These improvements were of clinical importance but were associated with a higher likelihood of serious adverse events.

Introduction Bronchoscopic lung volume reduction treatment with one-way valves is an effective guideline treatment option for patients with severe emphysema. However, important challenges and adverse reactions may occur after treatment. Areas covered This review summarizes the complications after endobronchial and intrabronchial valve treatment that have been described by the currently published randomized controlled trials and other relevant papers regarding the complications and its management. In case there was no relevant literature regarding these subjects, recommendations are based on expert opinion. Complications include pneumothorax, post-obstruction pneumonia and hemoptysis. Also, the treatment may not be effective due to the presence of collateral ventilation or misplaced valves. Furthermore, an initial beneficial effect may vanish due to granulation tissue formation, valve dysfunction or valve migration. Careful follow-up after treatment with valves is important. Evaluation with a CT-scan and/or bronchoscopy is needed if there is no improvement after treatment, loss of benefit, or occurrence of important adverse events during follow-up. Expert opinion Treating severe emphysema patients with one-way valves requires continuous dedication and expertise, especially to achieve an optimal outcome and elegantly deal with the various complications after treatment.

BACKGROUND: Reduced physical activity is common in COPD and is associated with poor outcomes. Physical activity is therefore a worthy target for intervention in clinical trials; however, trials evaluating physical activity have used heterogeneous methods. RESEARCH QUESTION: What is the available evidence on the efficacy and/or effectiveness of various interventions to enhance objectively measured physical activity in patients with COPD, taking into account the minimal preferred methodologic quality of physical activity assessment? STUDY DESIGN AND METHODS: In this narrative review, the COPD Biomarker Qualification Consortium (CBQC) task force searched three scientific databases for articles that reported the effect of an intervention on objectively measured physical activity in COPD. Based on scientific literature and expert consensus, only studies with ≥ 7 measurement days and ≥ 4 valid days of ≥ 8 h of monitoring were included in the primary analysis. RESULTS: Thirty-seven of 110 (34%) identified studies fulfilled the criteria, investigating the efficacy and/or effectiveness of physical activity behavior change programs (n = 7), mobile or electronic-health interventions (n = 9), rehabilitative exercise (n = 9), bronchodilation (n = 6), lung volume reduction procedures (n = 3), and other interventions (n = 3). Results are generally variable, reflecting the large differences in study characteristics and outcomes. Few studies show an increase beyond the proposed minimal important change of 600 to 1100 daily steps, indicating that enhancing physical activity levels is a challenge. INTERPRETATION: Only one-third of clinical trials measuring objective physical activity in people with COPD fulfilled the preset criteria regarding physical activity assessment. Studies showed variable effects on physical activity even when investigating similar interventions. ispartof: CHEST vol:160 issue:6 pages:2080-2100 ispartof: location:United States status: published

Introduction Bronchoscopic lung volume reduction with endobronchial valves is an important treatment option in selected patients with severe emphysema and absence of collateral ventilation in the treatment target lobe. The Chartis system provides an important physiological assessment of the presence or absence of collateral ventilation. We aimed to evaluate a new feature and determine whether low flow during a Chartis measurement is predictive for the absence of collateral ventilation, and whether this allows for a procedure to be shortened by earlier terminating the Chartis measurement. This is measured with the “volume trend for the previous 20 s” (VT20). Methods We retrospectively evaluated 249 Chartis assessments of patients scheduled for bronchoscopic lung volume reduction procedures. The VT20 was calculated, and several thresholds were compared between patients with collateral ventilation (CV positive) and without collateral ventilation (CV negative). Results 100% of the CV negative patients reached a threshold of VT20 ≤6 mL, whereas all CV positive patients reached a VT20 ≥7 mL. The median “time saved” between VT20=6 mL and end of assessment was 60 s (range 5–354 s). Conclusion The threshold of VT20 ≤6 mL is a reliable method to exclude the presence of collateral ventilation when air flow rates are low and can therefore reduce bronchoscopic lung volume procedure times., The volume trend for the previous 20 s (VT20) is an adjusted method of the Chartis measurement. This feature helps to interpret the Chartis measurement more easily and it effectively shortens the Chartis assessment time, especially in cases with low flow. https://bit.ly/3wlClxv

Chronic bronchitis is a chronic, progressive disease that is difficult to treat. Despite much effort, patients remain highly symptomatic. Currently, a number of innovative bronchoscopic treatments for this disease are under investigation. Liquid nitrogen metered cryospray, bronchial rheoplasty and balloon desobstruction all aim to destroy the hyperplastic goblet cells and excess submucous glands using different strategies. These therapies are in an early phase of clinical research and larger randomised controlled trials are needed to confirm the pilot data available and to evaluate the treatment durability. The fourth technique, targeted lung denervation (TLD), aims to decrease the release of acetylcholine, which regulates smooth muscle tone and mucus production by ablating the parasympathetic nerves running alongside the main bronchi. Evaluation of this treatment is at a more advanced stage and promising effects on exacerbation frequency have been shown. However, confirmation of the benefit in improvement in chronic bronchitis symptoms is still needed.

Severe emphysema patients who have been treated with endobronchial coils have been shown to initially benefit, but slowly decline in the years thereafter. Re-treating a patient with endobronchial coils could potentially lead to new improvements and may again reduce the rate of further decline. To our knowledge, until now, no results are published about patients who are re-treated. The primary aim of this study is to investigate the safety and feasibility of re-treating severe emphysema patients with endobronchial coils, using the PneumRx coil system. Furthermore, as secondary aim, we will evaluate the efficacy of re-treating these patients. Patients who at least 2 years ago were treated with endobronchial coils and responded clinically meaningful to this treatment were included in the study and re-treated. Safety was evaluated by the number of reported adverse events. Efficacy was evaluated 6 months after re-treatment, and measured by the change in quality of life, exercise capacity and pulmonary function testing. Eight patients were re-treated at a median of 1382 days (range 849-1545) after initial coil treatment with a median additional of 12 (10-15) coils per patient. During treatment, and until 6 months of follow-up, no unexpected adverse events occurred. Quality of life, exercise capacity and lung function did not change significantly 6 months after re-treatment. The results of this pilot study suggest that re-treating patients with endobronchial coils is feasible and safe. However, larger studies are needed to confirm these results and to investigate the efficacy and thus the clinical relevance.

COPD is diagnosed and evaluated by pulmonary function testing (PFT). Chest computed tomography (CT) primarily serves a descriptive role for diagnosis and severity evaluation. CT densitometry-based emphysema quantification and lobar fissure integrity assessment are most commonly used, mainly for lung volume reduction purposes and scientific efforts.A shift towards a more quantitative role for CT to assess pulmonary function is a logical next step, since more, currently underutilised, information is present in CT images. For instance, lung volumes such as residual volume and total lung capacity can be extracted from CT; these are strongly correlated to lung volumes measured by PFT.This review assesses the current evidence for use of quantitative CT as a proxy for PFT in COPD and discusses challenges in the movement towards CT as a more quantitative modality in COPD diagnosis and evaluation. To better understand the relevance of the traditional PFT measurements and the role CT might play in the replacement of these parameters, COPD pathology and traditional PFT measurements are discussed.

Background: Pneumothorax after bronchoscopic lung volume reduction using one-way endobronchial valves (EBVs) in patients with advanced emphysema occurs in approximately 20% of patients. It is not well known which factors predict the development of pneumothorax. Objective: To assess whether pleural adhesions on pretreatment high-resolution computed tomography (HRCT) scans are associated with pneumothorax occurrence after EBV treatment. Methods: HRCT scan analyses were performed on all patients who received EBV treatment in a randomized controlled trial. Three blinded readers scored adhesions by number and by measuring the longest axis of each pleural adhesion in the treated lung. The Pleural Adhesion Score (PAS) was calculated by adding 1 point for each small pleural lesion (5 mm). Results: The HRCT scans of 64 treated patients were assessed, of whom 14 developed pneumothorax. Patients who developed pneumothorax had a higher median number of pleural adhesions, 2.7 (IQR 1.9-4) compared to 1.7 (1-2.7) adhesions in the group without pneumothorax (p < 0.01). The PAS in the group with pneumothorax was higher compared to that in the group without: 14.3 (12.4-24.1) versus 6.7 (3.7-11.2) (p < 0.01). A threshold PAS of ≥12 was associated with a higher risk of pneumothorax (OR 13.0, 95% CI 3.1-54.9). A score Conclusion: A higher number of pleural adhesions on HRCT with a subsequent higher PAS in the treated lung is associated with a higher occurrence of pneumothorax after EBV treatment.

In patients with severe emphysema, bronchoscopic lung volume reduction using one-way valves is a promising therapeutic option to improve lung function and quality of life. The goal of this treatment is to achieve a complete lobar atelectasis. In a significant proportion of patients, this atelectasis cannot be achieved due to interlobar collateral ventilation. This collateral ventilation is generated through incomplete lobar fissures. Therefore, only patients with complete fissures and no collateral ventilation can be selected for endobronchial therapy with one-way valves. Incomplete fissures are very common and exhibit a great variation in anatomy. The reported prevalence is 17%-85% for the right major fissure, 19%-74% for the left major fissure, and 20%-90% for the minor fissure. There are several methods of measuring or predicting the presence of collateral ventilation, with computed tomography (CT)-fissure analysis and the Chartis measurement being the most important. CT-fissure analysis is an indirect method to measure the completeness of fissures as a surrogate for collateral ventilation. The Chartis system is an endobronchial method to directly measure the presence of collateral ventilation. Both methods have unique value, and the combination of both can accurately predict the treatment response to the bronchoscopic placement of endobronchial valves. This review provides an in-depth view of lung fissure and collateral ventilation to help understand its importance in selecting the appropriate patients for new emphysema treatments and thus avoid useless treatment in unsuitable patients.

Background: Adequate target lobe selection for endobronchial valve (EBV) treatment in patients with severe emphysema is essential for treatment success and can be based on emphysema destruction, lobar perfusion, lobar volume, and collateral ventilation. As some patients have >1 target lobe for EBV treatment, we were interested whether we could identify the least functional lobe. Objectives: The objective of this study was to investigate the relationship between endoscopic lobar measurement of oxygen uptake, lobar destruction, and vascular volume, and whether this could help in identifying the least functional lobe and thus optimal target for EBV treatment. Method: We prospectively included patients who were scheduled for EBV treatment in our hospital. A customized gas analysis setup was used to measure lobar O2 uptake after lobar balloon occlusion. Quantitative CT analysis was performed to assess the degree of emphysematous destruction and lobar arterial and venous volumes. Results: Twenty-one (5 male/16 female) patients with emphysema (median age 63 years, FEV1 25% of predicted, residual volume 234% of predicted) were included, and 49 endoscopic lobar measurements were performed. A lower O2 uptake significantly correlated with a higher degree of emphysematous lobar destruction (Spearman’s ρ: 0.39, p < 0.01), and lower arterial and venous vascular volumes of the lobes (–0.46 and –0.47, respectively; both p < 0.001). Conclusions: Endoscopic measurement of lobar O2 uptake is feasible in patients with emphysema. Measurement of lobar O2 uptake helped to identify the least functional lobe and can be used as additional tool for EBV target lobe selection.

Objective: To determine the impact of endobronchial coils on health-related quality-of-life (HRQoL). This paper utilizes trial data to identify the predictors of HRQoL in patients with severe emphysema, and subsequently estimates the impact of a new treatment on HRQoL (measured by utilities). These utility estimates are used to generate indicative long-term QALY estimates for a range of clinically plausible scenarios as a precursor to cost-effectiveness analyses.Methods: Patient level HRQoL data from RENEW and the National Emphysema Treatment Trial (NETT) were combined and mapped to generic EuroQol 5-dimension health utility questionnaire (EQ-5D) values using a published algorithm. Multilevel statistical models were developed using treatment, time, response, and baseline characteristics (EQ-5D, age, gender, FEV1, lung RV) to predict EQ-5D over time. Lifetime QALY estimates were generated using published survival data from NETT (assuming no impact of treatment on mortality) and four clinically plausible response profiles. Each response profile was combined with assumptions around treatment impact (constant or time varying).Results: After controlling for baseline characteristics, both treatment and response had a statistically significant impact (p Conclusions: Coils and SoC resulted in statistically significant improvements in HRQoL compared to SoC alone in patients with severe emphysema.

Background: Patients who achieve significant target lobe volume reduction (TLVR) following endobronchial valve (EBV) treatment may experience substantial improvements in clinical outcome measures. However, in cases of rapid TLVR, the risk of pneumothorax increases due to parenchymal rupture of the adjacent untreated lobe. Target lobe collapse may be more likely in EBV-treated patients who have low collateral ventilation. Objectives: The aim of this study was to evaluate the impact of pneumothorax on outcome following EBV treatment. Methods: Data from three prospective clinical trials (the US and European cohorts of VENT and the Multicenter Chartis study) were retrieved for the analysis. All patients had undergone chest X-ray within 24 h of EBV implantation to explore the presence of pneumothorax. TLVR was assessed at either 30 (Chartis study) or 180 days (VENT), and clinical outcome measures (forced expiratory volume in 1 s (FEV1), St. George's Respiratory Questionnaire (SGRQ) and 6-min-walk distance (6-MWD)) were assessed 180 days after implantation. Results: The overall rate of pneumothorax following valve therapy was 5.9% (25/421). Among these patients, 68% had a prolonged air leak for >7 days. However, patients who experienced a pneumothorax benefitted from EBV therapy, with a mean TLVR of 65% (n = 20). The mean percent change in FEV1 was 15 ± 15%, and the mean change in SGRQ was -7 ± 12 points. Conclusions: Although pneumothorax is a complication of EBV placement, it does not appear to have a negative impact on clinical outcome in terms of FEV1 and health-related quality of life.

Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease. Several studies have documented that long-acting bronchodilators can reduce exacerbation rate and/or severity, and others have shown that combinations of long-acting beta(2)-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA/inhaled corticosteroid combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single long-acting bronchodilators or LABA/inhaled corticosteroids in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus production with impairedmucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into this manuscript. Available clinical results support the possibility that effects of LABA/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. Although preclinical studies suggest LABAs and LAMAs have antiinflammatory effects, such effects have not been demonstrated yet in patients with chronic obstructive pulmonary disease.

Emphysema is characterised by airflow obstruction, hyperinflation, and resultant dyspnoea. It is worth investigating whether decompression improves lung mechanics and enhances quality of life (QoL).The purpose of this study was to describe the feasibility and safety of creating a transthoracic pneumostoma to enable lung reduction.A transthoracic 10-mm diameter Portaero Access Tube (Portaero™, Cupertino, CA, USA) was implanted via a third intercostal space incision in 15 severe emphysema patients [mean age 63 years, forced expiratory volume in 1 s 54% predicted, diffusing capacity for carbon monoxide 31% predicted, residual volume 246% predicted, Six-Minute Walk Test 296 m]. Four weeks later, an 8-mm Portaero Disposable Tube (3-8 cm in length) was substituted and changed daily thereafter. The targeted primary endpoints were a ≥12% increase in forced expiratory volume in 1 s and a decrease of ≥4 points in Saint George's Respiratory Questionnaire score at 6 months.Sixteen procedures were performed on 15 patients, complicated by 1 intercostal haemorrhage, 1 pneumothorax, and universal mild surgical emphysema. Early patency issues were common, but often responded to external endoscopic debridement or argon plasma laser. Three-month patency was achieved in 9 of 15 patients, and 6 of these had long-term patency (mean of 4 years). Patency was associated with potentially useful long-term improvements or stability in spirometry, residual volume, and QoL. However, the primary endpoints were not met at 6 months.The creation and maintenance of a transthoracic pneumostoma appears feasible and safe in patients with severe emphysema. Further studies refining patient selection (perhaps via chest computed tomography collateral ventilation and fissure assessments), techniques, and tube materials are suggested.

Chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), represent a major social and economic burden for worldwide health systems. During recent years, increasing attention has been directed to the role of small airways in respiratory diseases, and their exact contribution to the pathophysiology of asthma and COPD continues to be clarified. Indeed, it has been suggested that small airways play a distinct role in specific disease phenotypes. Besides providing information on small airways structure and diagnostic procedures, this review therefore aims to present updated and evidence-based findings on the role of small airways in the pathophysiology of asthma and COPD. Most of the available information derives from either pathological studies or review articles and there are few data on the natural history of small airways disease in the onset or progression of asthma and COPD. Comparisons between studies on the role of small airways are hard to draw because both asthma and COPD are highly heterogeneous conditions. Most studies have been performed in small population samples, and different techniques to characterize aspects of small airways function have been employed in order to assess inflammation and remodelling. Most methods of assessing small airways dysfunction have been largely confined to research purposes, but some data are encouraging, supporting the utilization of certain techniques into daily clinical practice, particularly for early-stage diseases, when subjects are often asymptomatic and routine pulmonary function tests may be within normal ranges. In this context further clinical trials and real-life feedback on large populations are desirable.

The St George's Respiratory Questionnaire (SGRQ) is a validated, commonly used questionnaire for measuring quality of life in patients with chronic obstructive pulmonary disease (COPD). The current established minimal important difference (MID) for SGRQ scores in an average COPD population is −4 units. However, for patients with severe COPD, the MID has not been thoroughly validated. We re-determined the SGRQ MID for this patient group.115 severe COPD patients (forced expiratory volume in 1 s (FEV1) 26±9% of predicted, SGRQ score 62±11 units; mean±sd,) who participated in seven different bronchoscopic lung volume reduction clinical trials were included in the analysis. Anchor- and distribution-based methods were used to define the MID for SGRQ scores. FEV1, 6-min walk distance and residual volume were used as anchors.Combining both anchor- and distribution-based methods, we identified a SGRQ MID of −8.3 units at 1 month and −7.1 units at 6 months.This study proposes an alternative SGRQ MID for patients with severe COPD of −8.3 units at 1 month and −7.1 units at 6 months follow-up after intervention. Our new MID estimates could be applied for both interpreting SGRQ outcomes as well as sample size determination in future clinical trials investigating interventions in severe COPD patients.

Patients with severe chronic obstructive pulmonary disease (COPD) suffer on a daily basis, despite important efforts to support this large patient population with pharmacotherapy. To potentially relieve symptoms, innovative bronchoscopic treatments have been developed in the past decade: the one-way endobronchial valve therapy for patients with severe emphysema and absence of interlobar collateral ventilation;1 the trans-bronchial airway bypass for severe emphysema, relying on the presence of collateral ventilation;2 nitinol coil treatment for a wide range of emphysema phenotypes independent of collateral ventilation;3 parasympathetic lung denervation for patients with COPD who respond well to anticholinergic agents;4 and sclerosing therapies such as crosslink compounds5 and steam,6 both of which target the most diseased parenchymal defects.